Stereoselective synthesis and structural analysis of polycyclic lactams derived from tetrahydroisoquinoline 1,2- And 1,3-diamines

Abstract

By means of the domino ring-closure reactions of (1S*,1 'S*)-1-(1′-aminoethyl)-, (1 R*,1 'R*)-1-(2′-amino- 1′-methylethyl)- and 1-(2-aminophenyl)-6,7-dimethoxy-1,2,3,4- tetrahydroisoquinoline with acyclic and aromatic γ- or δ-oxo acids, angularly-condensed tetra-, penta- and hexacyclic lactam derivatives were formed with practically full diastereoselectivities (de ∼100%), containing the substituents at the annelations of the saturated heterocyclic rings in cis position. The structure and relative stereochemistry of the products were determined with 1 H and 13C NMR spectroscopy. Further, the tetrahydropyridine ring (ring B) was observed to prefer cis fusion with the condensed imidazolidine or hexahydropyrimidine ring (ring C), with one exception preferring trans fusion (namely, the tetracyclic imidazolidine derivative bearing a methyl substituent at the C/D ring annelation, cmpd. 11). These two conformations can interconvert via simultaneous nitrogen inversion at the B/C annelation and ring inversion of the ring B, and their populations could be roughly estimated from the J-coupling constant data for each lactam derivative. The compounds gave fragment ions that were typical for the structures of the compounds. © ARKAT-USA, Inc.